Assessment of Natural Sunlight Protection Provided by 10 High-SPF Broad-Spectrum Sunscreens and Sun-Protective Fabrics.

In 1978, the FDA Advisory Panel proposed both indoor and natural sunlight SPF testing methods but reverted to indoor testing only in 1993. Today's sunscreen sun protection and broad-spectrum claims are based on mandated clinical tests using solar simulators and in vitro spectrophotometers. This research evaluated the protection of 10 high-SPF (30-110), broad-spectrum sunscreen products, as well as 6 sun-protective fabrics against natural sunlight in Arequipa, Peru. Each of the 17 subjects was exposed to natural sunlight for 1 h and 59 min under clear skies, with temperatures and humidity similar to those in an indoor clinical laboratory. Test sites were photographed 16-24 h later. Four dermatologists evaluated the photographs for erythema and persistent pigment darkening (PPD). Perceptible sun-induced skin injury (sunburn and/or pigmentation) was detected at 97% of the sunscreen-protected scores. The most sun-sensitive subjects obtained the least erythema protection. The higher the SPF was, the higher the erythema protection, but the intensity of PPD was also higher. The 2 sunscreens using only FDA-approved sunscreen filters rated 30 SPF and 45+ SPF performed poorly: Eighty-one percent of the 136 scores were graded 1 minimal erythema dose or higher erythema, achieving, at a maximum, SPF of 5-7 in natural sunlight. Sun-protective fabrics tested provided excellent sun protection. The erythema and PPD observed through the sunscreens in less than 2 h are incongruous with the broad-spectrum, high-SPF sunscreen claims. Reapplying these sunscreens and staying in the sun longer, as stated on the product labels, would have subjected the subjects to even more UV exposure. High-SPF, broad-spectrum sunscreen claims based on indoor solar simulator testing do not agree with the natural sunlight protection test results.

Homeostatic control of nuclear-encoded mitochondrial gene expression by the histone variant H2A.Z is essential for neuronal survival.

Histone variants are crucial regulators of chromatin structure and gene transcription, yet their functions within the brain remain largely unexplored. Here, we show that the H2A histone variant H2A.Z is essential for neuronal survival. Mice lacking H2A.Z in GABAergic neurons or Purkinje cells (PCs) present with a progressive cerebellar ataxia accompanied by widespread degeneration of PCs. Ablation of H2A.Z in other neuronal subtypes also triggers cell death. H2A.Z binds to the promoters of key nuclear-encoded mitochondrial genes to regulate their expression and promote organelle function. Bolstering mitochondrial activity genetically or by organelle transplant enhances the survival of H2A.Z-ablated neurons. Changes in bioenergetic status alter H2A.Z occupancy at the promoters of nuclear-encoded mitochondrial genes, an adaptive response essential for cell survival. Our results highlight that H2A.Z fulfills a key, conserved role in neuronal survival by acting as a transcriptional rheostat to regulate the expression of genes critical to mitochondrial function.

Cannabis, alcohol and other drug findings in fatally injured drivers in Ontario.

OBJECTIVE: The purpose of this study was to determine the prevalence of cannabis, alcohol and other drug use in drivers of motor vehicles who died in crashes in the Canadian province of Ontario from January 2016 through December 2018 along with the characteristics of these drivers and some of the circumstances of the crash in which they were involved. METHODS: Toxicological tests were performed on blood samples obtained from 921 driver fatalities for whom postmortem blood samples were submitted to the Center of Forensic Sciences for analysis. The results were coded into a database along with basic demographic and crash characteristics and examined for prominent characteristics and patterns. RESULTS: Overall, among the 921 cases examined, 495 (53.7%) tested positive for alcohol, cannabis (tetrahydrocannabinol or THC), or another psychoactive drug. The number of cases that tested positive for THC (251) exceeded the number of cases that tested positive for alcohol (241) as well as the number that tested positive for a drug other than THC (235). In 38% of positive cases, more than one substance was detected. Alcohol and THC were most commonly detected among males; females most frequently tested positive for a drug other than THC, notably medications with depressant effects. Alcohol-involved driver fatalities were most common on weekends and most likely involved single vehicle crashes. Driver fatalities that tested positive for THC or another drug were more evenly distributed throughout the week and were more likely to have been in multi-vehicle crashes. CONCLUSIONS: The present study highlights the use of cannabis and other drugs by drivers. The patterns of crashes and the characteristics of drivers involved indicate that the characteristics of driver fatalities involving cannabis and/or other drug use differ from those of alcohol and require new, innovative approaches targeting high-risk times, groups and behaviors. Continued monitoring of the toxicological findings from blood samples obtained from drivers killed in motor vehicle crashes will be a key element in efforts to reduce the impact of drug use by drivers on road safety.

Volume restoration of hands with polycaprolactone by cannula delivery; a prospective single center consecutive case series evaluation.

Background: Dorsal hand volume loss results in the perception of aging appearance. Several volumizing fillers have been used for this correction.Objective: To report restoration of dorsal hand volume using cannula delivery of Polycaprolactone (PCL) microspheres and to assess efficacy, duration, and safety up to 3 years post treatment.Method: Fifteen patients with volume loss of their hands were evaluated by clinical examination, photography and a hand volume grading scale. PCL was injected by 25 G cannula after locating dorsal veins using a viewing laser to avoid intravascular injections. Patients' satisfaction and grade of severity were reevaluated at early (3-6 months) and late (12-18 months) timepoints following the procedure. A second treatment was offered if desired by the patient.Results: Eight participants required one treatment session to achieve satisfaction. Five had two treatments. Patients requiring a second treatment were reassessed after 12 months. All patients had improvements on the severity score by the end of the evaluation period. Side effects were minimal and transient. No patients developed bruising.Conclusion: PCL injections are reliable method for hand volumization. Results persisted for up to 3 years in some patients. Laser vein viewer and cannula delivery ensure uniform injections and avoid intravascular injuries.

Photodynamic Therapy: A Clinical Consensus Guide.

BACKGROUND: The American Society of Dermatologic Surgery (ASDS) periodically develops consensus documents for its members concerning various aspects of dermatologic surgery. Advances in photodynamic therapy (PDT) have been many and PDT use has been established in a variety of skin conditions. OBJECTIVE: The ASDS board of directors proposed a committee of experts in the field to develop consensus documents on different treatments. An expert panel reviewed the literature on PDT and discussed the findings. The consensus was reached with evidence-based recommendations on different clinical applications for PDT. PATIENTS AND METHODS: This consensus document includes discussions regarding PDT, including different photosensitizers and various light source activators, historical perspective, mechanism of action, various therapeutic indications and expected outcomes, pre- and post-care, and management of adverse outcomes. RESULTS: Photodynamic therapy is highly effective for pre-cancerous lesions, superficial nonmelanoma skin cancers, inflammatory acne vulgaris and other conditions. New protocols including laser mediated PDT significantly improve results for several indications. CONCLUSION: The ASDS consensus document on PDT will be helpful for educating members on safe and effective PDT for a variety of indications.

Botulinum toxin type B: pH change reduces injection pain, retains efficacy.

BACKGROUND: Injection of botulinum toxin Type B (BTX-B) is substantially more painful than injection of botulinum toxin Type A (BTX-A). OBJECTIVE: A method of reducing pain with BTX-B injection without reducing efficacy. This was evaluated in 2 BTX-A-resistant subjects and another BTX-B-naive subject. METHODS: Clinical evaluation and computer analysis of photographs were used to confirm efficacy to different dilutions of Type B toxin and confirm BTX-A resistance. A pilot study of 3 subjects involves BTX-B (usually pH 5.6) that was diluted with sodium bicarbonate to normalize the pH to 7.5 in the syringe immediately before injection. Pain assessment compared the different pH BTX-B solutions. RESULTS: Two patients with acquired resistance to 3 BTX-As in upper facial muscles responded to BTX-B. Injection pain of BTX-B changed to pH 7.5 was significantly reduced and retained efficacy over 10 weeks. CONCLUSION: Botulinum toxin Type A resistance is documented to 3 BTX-A brands in 2 patients. They had received low doses of Type A toxin, they responded to Type B toxin. Injection pain of the acidic solution of BTX-B neurotoxin was reduced and efficacy not compromised by changing pH of BTX-B solution to pH 7.5. This method improved patient tolerance to BTX-B injections.

Botulinum toxins for facial lines: a concise review.

This is a concise review of the uses of botulinum toxins (BTXs) in dermatology and cosmetic procedures. It is a clinical rather than a basic science, pharmacological review. BTX had been initially used for selectively reducing and balancing periorbital muscle activity; thereby, reducing childhood strabismus and blepharospasm. This clinical research was initiated by Dr. Alan Scott over 40 years ago. BTX type A (BTX-A) was serendipitously observed to reduce forehead frown lines in patients being treated for blepharospasm. Extensive clinical research and development resulted in widespread aesthetic uses for BTX-A by reduction of selected hyperfunctional facial muscles. BTXs are also used for reduced localized hyperhidrosis. A topical BTX-A is being developed as a potential alternative to injected BTX.

Four methods of evaluation of facial erythema and pigment treated with intense pulsed light or cream.

AIM: To evaluate methods of evaluation of patients with mild to moderate facial pigmentation or erythema and compare clinical and photographic grading with instrumental evaluation. METHODS: Of the 24 female subjects treated, 12 were treated with intense pulsed light (IPL) and 12 were treated with daily cream program. Evaluations before and at 16 weeks consisted of: 1. Clinical examination and severity grading by a dermatologist without knowledge of treatment given. 2. Standardised photographs were evaluated by two other dermatologists without knowledge of treatment given. 3. A computer controlled photographic skin analysis systems was used to grade severity of erythema and pigmentation. 4. Subjects were asked to assess their response at the end of a 16-week period, that is, subject self-evaluation. RESULTS: On clinical evaluation of IPL subjects, 12 showed improvement. Of the cream subjects, 11 showed improvement. There was correlation between dermatologist facial examination and the instrumental method. Overall the different assessments showed a slightly greater trend for improvement with IPL treatments for erythema and pigmentation, but no statistical differences were found between the treatments using Student's t-test and Anova analysis of comparative improvement.

Investigator global evaluations of efficacy of injectable poly-L-lactic acid versus human collagen in the correction of nasolabial fold wrinkles.

BACKGROUND: Injectable poly-L-lactic acid (PLLA) is indicated in the United States for use in immune-competent patients for correction of shallow-to-deep nasolabial fold contour deficiencies and other facial wrinkles in which a deep dermal grid pattern injection technique is appropriate. It is also indicated for restoration and/or correction of signs of lipoatrophy in patients with human immunodeficiency virus. OBJECTIVE: The authors examine the efficacy of injectable PLLA for correction of nasolabial fold wrinkles, based on Investigator Global Evaluations (IGE). METHODS: A randomized, multicenter, subject-blinded, parallel-group study compared injectable PLLA versus human collagen for correction of nasolabial fold wrinkles for 13 months after up to four treatments (intent-to-treat population, 233). Injectable PLLA-treated subjects were followed up for an additional 12 months (total, 25 months) after the final treatment session. Efficacy was also assessed through secondary IGE for improvement, which is the subject of this report. RESULTS: IGE reports of improvement were significantly greater in subjects who received injectable PLLA versus those who received human collagen (p < .001). Overall improvement with injectable PLLA was 100% three weeks after the final treatment, remaining above 85% through month 25. Overall IGE of improvement with human collagen declined from 94.0% at week three to 6.0% at month 13. Both treatment groups had similar safety profiles. CONCLUSIONS: IGE of improvement were significantly greater with injectable PLLA treatment than with human collagen treatment at all time points following the last treatment. Injectable PLLA treatment continued to show a beneficial effect for up to 25 months.

Subject global evaluation and subject satisfaction using injectable poly-L-lactic acid versus human collagen for the correction of nasolabial fold wrinkles.

BACKGROUND: This is a report of the secondary endpoints, Subject Global Evaluation (overall improvement) and Subject Satisfaction scores, from a study designed to examine the efficacy of injectable poly-L-lactic acid for the correction of nasolabial fold wrinkles over 25 months. METHODS: A randomized, subject-blinded, parallel-group, multicenter clinical study was conducted to compare the effects of injectable poly-L-lactic acid with those of human collagen for the treatment of nasolabial fold wrinkles at 13 months following the last treatment. Injectable poly-L-lactic acid-treated subjects were followed for 25 months. RESULTS: From month 3 through month 13 following the last treatment, injectable poly-L-lactic acid-treated subjects (n = 116) reported significantly higher Subject Global Evaluation scores compared with human collagen-treated subjects (n = 117; p < 0.001). Overall Subject Global Evaluation scores for injectable poly-L-lactic acid-treated subjects were 99 percent at week 3, 91 percent at month 13, and 81 percent at month 25 (all times following the last treatment). In contrast, for human collagen-treated subjects, overall Subject Global Evaluation scores declined by 84 percent, from 96 percent at week 3 to 15 percent at month 13. Subject Satisfaction scores were significantly different (p < 0.01) between treatment groups beginning week 3 and continuing through month 13. Overall Subject Satisfaction scores were maintained for over 80 percent of injectable poly-l-lactic acid-treated subjects (n = 106) at month 25 after the last treatment. CONCLUSIONS: Treatment of nasolabial fold wrinkles with injectable poly-l-lactic acid resulted in statistically significantly higher Subject Global Evaluation and Subject Satisfaction scores compared with human collagen at 13 months. Injectable poly-l-lactic acid-treated subjects maintained improvements for up to 25 months after treatment.

Three-dimensional digital surface imaging measurement of the volumizing effect of injectable poly-L-lactic acid for nasolabial folds.

INTRODUCTION: Injectable poly-l-lactic acid (PLLA) is a biocompatible and biodegradable polymer device indicated in Europe for correction of facial contour deficiencies, with a gradual onset of effect that is maintained for up to 25 months. METHODS: In this single-centre, open-label study, 20 adult subjects seeking treatment for facial contour deficiencies were treated with injectable PLLA every 4-6 weeks for ≤6 months or until optimal correction (0 or 1 on nasolabial photonumeric wrinkle assessment scale [0 = no wrinkles; 5 = very deep wrinkles, redundant fold]). 3-D digital surface imaging and standardized 2-D photography were used to assess mid-face and nasolabial volumetric correction and clinical improvement, respectively. RESULTS: Based on 3-D digital surface imaging, statistically significant increases in average mid-facial volume occurred with injectable PLLA after the first injection session and persisted through to the end of treatment. Investigator and subject ratings of 'much improved' or 'excellent' improvement were reported using 2-D photographs as a visual aid. Subjects reported high levels of satisfaction. No serious adverse events were reported. DISCUSSION: In this study, injectable PLLA was found to be safe and effective for mid-face and nasolabial fold volumetric correction.

A phase IIa open-label dose-escalation pilot study using allogeneic human dermal fibroblasts for nasolabial folds.

BACKGROUND AND OBJECTIVE: The correction of soft tissue contour defects and dermal atrophy is a growing area driven by medical and aesthetic need. Deterioration of the skin's appearance occurs as a result of age and trauma, such as surgery, infections, and acne. Typically, imperfections are treated with volume-correcting fillers. This study evaluated allogeneic human dermal fibroblasts (HDFs) for the treatment of nasolabial folds as an alternative strategy to improve the structure, texture, and quality of the skin. METHODS AND MATERIALS: In this phase IIa study, a suspension of allogeneic HDF (2 × 10(6) cells/mL or 2 × 10(7) cells/mL) was injected intradermally along the nasolabial fold; line severity was assessed using a photographic scale. RESULTS: Mean investigator satisfaction was 7.4 (range 4.7-9.5) at 12 weeks and 7.6 (range 4.4-9.8) at 24 weeks. Subject satisfaction scores were 7.0 (range 0.1-10.0) at 12 weeks and 7.8 (range 1.5-10.0) at 24 weeks. All patients experienced adverse events, the majority of which were deemed treatment related. Most were mild to moderate in severity and resolved completely. CONCLUSION: This study demonstrated that allogeneic HDF can produce an improvement in aesthetic appearance with minimal adverse events and warrants further investigation and development. Intercytex provided financial support for this study. John Roberts is an employee of Intercytex.

Dosing, efficacy and safety plus the use of computerized photography for botulinum toxins type A for upper facial lines.

INTRODUCTION: Several studies confirm that botulinum toxins type A (BTX-A) are effective for reducing facial lines caused by hyperactive muscles. Two different commercial types of BTX-A currently available are BTX-A-1 (Botox) and BTX-A-2 (Dysport). This paper reports further comparison of dosing, efficacy and safety. METHODS: Sites treated: glabellar, horizontal forehead lines and crow's feet. Different dilutions and dosages were studied with BTX-A-1 and BTX-A-2. The reduction of facial lines was evaluated by investigators and patients. Computerized photographic numerical assessment was also studied in determining the efficacy of BTX-A for crow's feet lines. RESULTS: Study 1: Injecting glabellar lines at doses of BTX-A-1 (30 units) and BTX-A-2 (75 units) (2.5:1 ratio BTX-A2:BTX-A1) showed similar efficacy. Study 2: BTX-A-2 (256 units total) was significantly more effective than BTX-A-1 (64 units total) (i.e. a dose ratio of 4:1) for upper face lines. No differences in the side-effect profiles between the two toxins were observed in either study. Study 3: A computerized photographic numerical assay was an objective assessment of crow's feet severity. Using a dose ratio of BTX-A-2 to BTX-A-1 of 3:1 showed a trend towards BTX-A-2 superiority. CONCLUSION: Two different botulinum toxins type A were shown to be effective and safe for hyperfunctional facial lines. The choice of dose, dilution and placement is critical for each individual toxin. Computerized photography gave numerical severity scores of crow's feet severity.

A randomized study of the efficacy and safety of injectable poly-L-lactic acid versus human-based collagen implant in the treatment of nasolabial fold wrinkles.

BACKGROUND: Injectable poly-L-lactic acid (PLLA) is a synthetic, biodegradable, biocompatible polymer device. OBJECTIVE: We sought to compare the efficacy and safety of injectable PLLA with human-derived collagen in treating nasolabial fold wrinkles. METHODS: In this randomized, evaluator-blinded, parallel-group, multicenter study, subjects received injectable PLLA (n = 116) or collagen (n = 117) injections (1-4 visits, 3-week intervals). Wrinkle Assessment Scale scores were calculated at screening; posttreatment week 3; months 3, 6, 9, and 13 (injectable PLLA or collagen groups); and months 19 and 25 (injectable PLLA group). Safety data were obtained from subject interviews and case report forms. RESULTS: Injectable PLLA significantly improved mean Wrinkle Assessment Scale scores (all time points, P < .001). Improvements (up to 25 months after last treatment) were significantly greater (P < .001) than with collagen for posttreatment months 3 to 13. LIMITATIONS: Mostly white women and subjects with Fitzpatrick skin types II and III were included. CONCLUSION: Injectable PLLA provides well-tolerated, effective, and long-lasting (up to 25 months) nasolabial fold wrinkle correction.

Injectable poly-L-lactic acid for cosmetic enhancement: learning from the European experience.

Currently a diverse range of injectable agents are used for noninvasive facial enhancement. Injectable poly-L-lactic acid (PLLA) is a biocompatible, biodegradable, synthetic polymer that is approved for correction of HIV-related facial lipoatrophy in Europe, Canada, and the United States. PLLA is also approved in several countries for cosmetic purposes, and is under review in the United States for this indication. After injection, PLLA elicits a gradual increase in facial volume via hypothesized endogenous production of fibroblasts and, subsequently, collagen, enabling global facial rejuvenation to be tailored, as required, over time. Substantial increases in dermal thickness after injection of PLLA have been observed to last for up to 2 years. This article reviews the use of PLLA in Europe and the United States with regard to practitioner experiences and techniques for optimizing outcomes. Correct reconstitution and administration of PLLA have been found to be important parameters for optimal use of this agent.

Injectable poly-l-lactic acid: 3 years of aesthetic experience.

BACKGROUND: Injectable poly-l-lactic acid (PLLA) has been used to correct age- or disease-related facial volume deficits. OBJECTIVE: This single-center, retrospective survey evaluated PLLA for cosmetic use. METHODS AND MATERIALS: A questionnaire was mailed to 281 patients treated with PLLA 6 months or more previously. PLLA was reconstituted 4 hours or more before injection with 5 mL of sterile water plus 1 mL of 1% xylocaine added before injection. RESULTS: Two hundred twenty-one patients responded (210 female; average age 54.3; average treatments 3.3 per patient); the majority had received facial injections. Transient side effects included bruising, swelling, and discomfort. After treatment (1-6 months), 14/41 patients developed Grade 1 papules or nodules (slightly palpable, nonvisible; clinically nonrelevant; all resolved spontaneously), 15/41 developed Grade 2 papules or nodules (palpable, slightly visible; clinically nonrelevant; all resolved spontaneously), and 12/41 developed Grade 3 nodules (easily palpable, obviously visible [9 perioral; 3 periorbital or temple]; 5 resolved spontaneously; 7 were treated [5 intralesional corticosteroids; 2 surgery]). CONCLUSION: Patients treated with PLLA experienced duration of improvement of up to 24 months. Maximum improvement took several treatment sessions. Nodules occurred in perioral and periorbital regions, so incidence is reduced by avoiding these areas.

Photodynamic therapy with methyl aminolevulinate for primary nodular basal cell carcinoma: results of two randomized studies.

BACKGROUND: Data suggest that photodynamic therapy using topical methyl aminolevulinate (MAL PDT) may be a noninvasive alternative to excisional surgery for nodular basal cell carcinoma (BCC). In the studies described here, we investigated the histologic response, tolerability, and cosmetic outcome with MAL PDT for primary nodular BCC (or= 50% reduction in greatest diameter) at 3 months were re-treated (21%). Treatment sites were excised at 3 months (clinical nonresponders) or 6 months (clinical responders) after the last treatment. RESULTS: Histologically verified lesion complete response rates were higher with MAL PDT than with placebo [73% (55/75) vs. 27% (20/75)]. Treatment was most effective for facial lesions (89% complete response). Cosmetic outcome was good or excellent in 98% of evaluable, completely responding lesions treated with MAL PDT. CONCLUSION: Although longer follow-up studies are required, these promising data indicate the potential of topical MAL PDT as a noninvasive treatment alternative for nodular BCC.

Comparisons among botulinum toxins: an evidence-based review.

BACKGROUND: Botulinum neurotoxin treatment is the most common aesthetic procedure in the United States. A number of serotypes and formulations are available worldwide. Similarities and differences among these toxins were evaluated by reviewing the existing literature. METHODS: Reports of botulinum neurotoxin for aesthetic use, published in peer-reviewed literature or presented at recent professional congresses, were reviewed to summarize key features of different toxins. Data from therapeutic uses in comparable anatomical areas were included in the review when aesthetic literature was limited. RESULTS: Serotypes of neurotoxins share molecular structures and mechanisms of action but exhibit important differences between serotypes and between different formulations within the same serotype, including differences in distribution/diffusion patterns and risk/benefit profiles. The differences attributable to dissimilarities in bacterial strains, manufacturing techniques, and assays are likely to influence clinical performance. CONCLUSIONS: Injection patterns, techniques, dilutions diffusion, and injection volumes established for a specific formulation of botulinum neurotoxin are not likely to be applicable to other formulations, and formulations are not interchangeable by any single conversion ratio. A large proportion of the clinical literature documents the aesthetic uses of the Allergan formulation of botulinum toxin type A. Additional studies are needed to establish optimal procedures for the Ipsen formulation and botulinum neurotoxin, and for diverse aesthetic uses.

Etanercept therapy allows the tapering of methotrexate and sustained clinical responses in patients with moderate to severe psoriasis.

Methotrexate, the most common systemic small molecule used in the treatment of moderate to severe psoriasis, is associated with significant toxicities and adverse events. Long-term continuous usage is not recommended due to potential liver toxicity, myelosuppression, and other side effects. Abrupt cessation of methotrexate without tapering can lead to flare-up and rebound of psoriasis. Here we describe sustained clinical responses in 6 patients with psoriasis following gradual cessation of methotrexate through the addition of etanercept therapy.

Facial aesthetics: achieving the natural, relaxed look.

When patients undergoing nonsurgical facial rejuvenation procedures are asked to state their expectations in terms of outcomes, the achievement of a "natural, relaxed look" usually emerges as the paramount goal. The importance to clinicians of delivering on this patient desire is becoming increasingly clear. After all, patient satisfaction is the ultimate treatment goal. This article explores aspects of what defines the natural, relaxed look and what patients are seeking when they undergo nonsurgical facial rejuvenation procedures and is based on the clinical experience of the authors. The article also offers suggestions intended to help clinicians provide each patient with appropriate outcomes and satisfaction.